Resin bound dynamic combinatorial chemistry (“RBDCC”) alleviates common problems associated with traditional solution phase dynamic combinatorial chemistry. In the RBDCC approach, immobilized library constituents are spatially segregated on a solid support and allowed to equilibrate with library constituents in solution via reversible bond formation. This solid phase immobilization thereby eliminates the need for chromatographic solution separation during dynamic combinatorial library (“DCL”) analysis. Expanding on the utilization of phase separations in dynamic combinatorial chemistry (Klekota et al., “Generation of Novel DNA-binding Compounds by Selection and Amplification from Self-assembled Combinatorial Libraries,” Tetrahedron Letters 38:8639-8642 (1997); Whitney et al., “Templated Ligand Assembly by Using G-quadruplex DNA and Dynamic Covalent Chemistry,” Angewandte Chemie International Edition English 43:1143-1146 (2004), each of which is hereby incorporated by reference in its entirety), RBDCC represents the first example of phase tagging library members (McNaughton et al., “Resin-bound Dynamic Combinatorial Chemistry,” Organic Letters 8:1803-1806 (2006), which is hereby incorporated by reference in its entirety). The RBDCC screening procedure utilizes a labeled target. When the library is screened against a fluorescently labeled target, any immobilized library member that binds the target is easily visualized, spatially separated, and identified by mass spectrometry, greatly simplifying DCL analysis.
The present invention is directed to the identification of compounds that are capable of modifying the activity of target RNA molecules associated with a particular disease state, and therefore also capable of treating those disease states.